IMMUNE SYSTEM-ON-A-CHIP FOR QUANTITATIVE ANALYSIS OF CELL INTERACTIONS DURING ALLERGY RESPONSE Abstract The human immune system is an elaborate and dynamic network of cells, tissues, and organs responsible for protecting us from disease. Understanding the fundamental cellular interactions in vivo during immune response is a daunting task based on the inherent complexity of similar but distinct cell types and the diverse signaling pathways between these cells. The work proposed herein exploits a bottom-up analysis strategy, first using microelectrochemistry techniques to quantitatively characterize chemical messenger secretion from individual immune cells in real time, then characterizing how this degranulation response changes with controlled exposure to various triggering molecules and chemokines, and finally assembling a simplified immune-system-on-a-chip where direct cell-cell communication can be measured, controlled, and manipulated. This work will reveal both useful fundamental information about chemical messenger packaging and delivery in immune system cells and illuminate the mechanism of and possible therapeutic approaches to Type I hypersensitivity using the interconnected chip-based format. This work is particularly well-suited to the NIH New Innovator funding mechanism based on the fact that this is a high risk-high reward project that, if successful, will have a major impact on biomedical science. Additionally, this interdisciplinary approach, requiring not only non- traditional methods but also a paradigm shift where immune cell interactions are considered from a bottom-up perspective, can only be executed with significant financial support and the freedom to achieve great results based on encouraged innovation and creativity. The risk of this innovative proposal is mitigated by the fact that initial experiments commence directly from preliminary results in the Haynes laboratory and complexity is added at each major step. In addition, the principle investigator has a performance history of leveraging her expertise in an entirely new field, allowing her research group to approach scientific problems in a way nobody else is considering and provide insight with new perspective.